Pregnancy has lasting adverse effects on correlates of insulin resistance including excess weight gain and abdominal obesity, as well as lower plasma high density lipoprotein cholesterol (HDL-C) persisting for several years, as first reported by this investigator. Moreover, lactation has been shown to increase insulin sensitivity and have favorable effects on lipoprotein profiles in women within one year postpartum. Genetic factors influence the associations between sex hormone exposures and lipoprotein levels in women, but the relationship to pregnancy (endogenous sex hormones) has not been evaluated. This study will examine the associations of childbearing with changes in correlates of insulin resistance: indexes of insulin resistance, SHBG, CRP, HDL-C, and total and central adiposity. We hypothesize the following: 1) Pregnancy will be associated with less favorable changes in correlates of insulin resistance. Primary Aim 1: One or more births versus none during follow-up will be associated with larger increments in indexes of insulin resistance, CRP, and visceral and total body fat, and with larger decrements in SHBG; 2) Lactation will be associated with more favorable changes in correlates of insulin resistance among parous women. Primary Aim 2: Lactation will be associated with smaller increments in indexes of insulin resistance, body weight, and waist girth, and smaller decrements in SHBG and HDL-C; and 3) Secondary Aim: Genetic polymorphisms Apolipoprotein E will modify the HDL-C declines associated with primiparity. We plan to utilize two existing sources of prospectively collected data from biracial (50% African American and 50% Caucasian), population-based samples of women of reproductive age: the NHLBI Growth and Health Study (NGHS), and the Coronary Artery Disease in Young Adults (CARDIA) Study. These data sources are unique in the availability of preconception measurements, and internal comparison groups of nongravid women. Our findings will form the basis of R01 proposals to evaluate pregnancy and lactation in relation to disease endpoints such as metabolic syndrome, subclinical coronary artery disease, and diabetes from the year 20 CARDIA exam, and propspective studies of lactation and prevention of type 2 diabetes in women with previous gestational diabetes. The K01 two-year renewal training plan includes mentoring from sponsor (Dr. B. Caan) and co-sponsor (Dr. S. Sidney), continued training in genetic epidemiology (Dr. N. Risch), training in body composition assessment, grant-writing, and coursework in hormonal pathways involved in long-term control of body weight. appetite and energy balance. Findings from this study will enhance our understanding of pregnancy's lasting effects on women's health including weight gain, and the risk of heart disease and diabetes. The study will also assess whether breastfeeding has beneficial effects on risk factors that may help prevent heart disease and diabetes in women.